Abstract | OBJECTIVE: To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset. METHODS: Three patients with mutations in DARS were identified by combining MRI pattern recognition and genetic analysis. RESULTS: One patient had the typical infantile presentation, but 2 patients with onset in late adolescence had a disease mimicking an acquired inflammatory CNS disorder. Adolescent-onset patients presented with subacute spastic paraplegia and had positive response to steroids. They had only minor focal supratentorial white matter abnormalities, but identical spinal cord changes involving dorsal columns and corticospinal tracts. Clinical presentation included subacute spastic paraplegia with partial improvement on steroids. CONCLUSIONS: Focal T2 hyperintense white matter changes on brain MRI in combination with spinal cord signal abnormalities usually suggest acquired inflammatory conditions such as multiple sclerosis, especially in the context of relapsing course and a positive response to steroid treatment. Adolescents with mutations in DARS can present with a comparable clinical picture, broadening the clinical spectrum of hypomyelination with brainstem and spinal cord involvement and leg spasticity.
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Authors | Nicole I Wolf, Camilo Toro, Ilya Kister, Kartikasalwah Abd Latif, Richard Leventer, Amy Pizzino, Cas Simons, Truus E M Abbink, Ryan J Taft, Marjo S van der Knaap, Adeline Vanderver |
Journal | Neurology
(Neurology)
Vol. 84
Issue 3
Pg. 226-30
(Jan 20 2015)
ISSN: 1526-632X [Electronic] United States |
PMID | 25527264
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 American Academy of Neurology. |
Chemical References |
- Steroids
- Lactic Acid
- Aspartate-tRNA Ligase
- DARS2 protein, human
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Topics |
- Age of Onset
- Aspartate-tRNA Ligase
(genetics)
- Cerebral Cortex
(pathology)
- Databases, Factual
- Encephalitis
(physiopathology)
- Female
- Humans
- Infant
- Lactic Acid
(metabolism)
- Leukoencephalopathies
(complications, diagnosis, drug therapy, genetics)
- Magnetic Resonance Imaging
- Male
- Muscle Spasticity
(etiology)
- Mutation
(genetics)
- Spinal Cord
(pathology)
- Steroids
(therapeutic use)
- Young Adult
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